Future cancer care, and the cost of large animal extinction
In this episode, why approaches to cancer care need a pro-active approach in future, the opportunities arising for the cancer vaccine space, competency-based medical training, the environmental costs of losing large animals, and why water resilience needs careful planning now...
In this episode
00:42 - What's the future of cancer care?
What's the future of cancer care?
Andrew Bassim Hassan, University of Oxford
The sobering statistic is that roughly one in every two of us will have a brush with cancer at some point in our lives, and as the world population continues to grow, and the population ages, the burden of malignant disease is destined to inflate significantly. At the moment, with a few exceptions where there are screening programmes for conditions like breast cancer, we operate chiefly a reactive response to the disease: when we pick it up, we then launch into a - usually very expensive - programme of treatment that can have variable outcomes. This, as Oxford University oncologist Andrew Bassim Hassan argues to Chris Smith, needs to change. We need to become much better at preventing and picking up cancer in the first place, and we need to do it by embracing new technology and data tools. Expensive, yes, but, he suggests, probably not much more so than the money we already spend reactively at the end of someone's life. So why not bite the bullet and front-load the equation, aiming to keep people healthier for longer...
Andrew - We have an increasing global population and an increasing age of that global population. That immediately converts into an increased incidence and prevalence of cancer across the globe. Different cancers, different subtypes of the same cancer in different people with different physical and genetic makeup.
Chris - So if one looks at lists like those that the WHO publish of morbidity and mortality around the world, where on that list does cancer sit as a cause of loss of life globally?
Andrew - It's not the highest. The highest is mainly infectious diseases, but cancer is one of those key elements along with cardiovascular disease that is increasing steadily and is quite a significant disease burden worldwide.
Chris - And what opportunities in this era now present themselves to us, given what you've just said in terms of how we might be able to make inroads against what we foresee to possibly be at the top of that list in the future?
Andrew - We've got to think about cancer from all different perspectives. From a preventative perspective, screening and intensively monitoring people who may be at high risk of developing a cancer in order to try and catch the cancers early on in the disease process offers up the best opportunity for cure and long-term survival. If we rely on a strategy that starts to intervene with cancer very much late in its process where it may have already spread to other sites in the body, we may be pouring a huge amount of effort and resources into a problem that we're already realising is very difficult to solve. And that latter strategy is very expensive.
Chris - If I were the health minister and I came to you and said, right, I want to make cancer a priority and I want to take away a lot of the barriers that confront you at the moment to delivering really exceptional cancer care and affecting cures in as many cases as we can, but control in the rest, what would be on that list then of things that you would be saying to me, 'I need to surmount the following problems, or I need resourcing of the following areas to do that?'
Andrew - The current UK government have probably got it right in that the emphasis does need to move to early diagnosis and prevention. I would want a screening system that incorporates the modern technologies such as genome sequencing, both of the person as well as the DNA that has emerged in the cancer. That information, integrated with the healthcare record scans, imaging, all of that needs to be brought right forward into the pathway. Through that strategy, we will have a better chance of intervening earlier with new technologies that are also emerging, such as cancer vaccines, in order to prevent patients progressing all the way down to the spread of the disease. Now to do that, you've got to move to a new model. How you do that will require a step change of investment in order to get it working. That includes data, how you connect all that information together, and how you make sure that's protected, analysed properly, and the right decisions made from that information.
Chris - A lot of this hinges on a personalised approach to this, doesn't it, especially where the DNA aspects are concerned. But this is very expensive. Screening people in this way, having people who are really good at interpreting the results of those screens, admittedly AI can help us a bit there and help to weed out some cases, but this is very, very expensive. How do you see us dealing with the economics of all of this, because the world population is going up not down and, as you say, it's an ageing population where this is going to become more common, not less.
Andrew - Well, the first thing to cover is that we spend the majority of our healthcare budget, be that for cancer or anything else, in the last six months of life. We try and stem a disease process that's taken years to develop and we are finding it very difficult to overcome that, to reverse that. In fact, some people would say it's impossible to reverse some of those. So I think we need to think differently and move the money around. I think it exists within the system. That's the first thing to say. The second thing to say is that the costs of some of these tests have dramatically fallen. To sequence your whole genome now costs about £300. That's the cost of a mobile phone or a flight to Paris. If we think in those terms, and we start to think about the scale of cancer, maybe up to 50% of us in our lifetime, then you can get the sort of feel that in fact the cost benefit equation looks actually really good. It's because the cost of these tech developments have dramatically fallen. I think the economic argument is very strong. I think this is actually a cost effective solution. This is actually going to save money if we play this correctly.
07:30 - The opportunity posed by cancer vaccines
The opportunity posed by cancer vaccines
Leonard Lee, University of Oxford
One treatment that is fast gaining momentum in the cancer therapy world is vaccination; I don't mean initiatives like the incredibly successful cervical cancer vaccine programme, which prevents infection with the human papilloma virus that causes cervical and some head and neck cancers. Actually, I'm referring to the approach where scientists can now identify characteristic markers on cancer cells that are unique to the tumour and not present on healthy cells. By targeting the immune response at these signatures using new approaches like the mRNA vaccine technologies road tested for the first time in humans during the COVID pandemic, great strides might be made in stopping a person's cancer coming back. As he explains to Chris Smith, oncologist Leonard Lee, from Oxford University, has identified in the healthcare system a list of strengths we can capitalise on and some missing elements that we need to reinforce to make the most of the opportunity that this new technology can offer...
Len - Vaccines prevent disease and in many ways cancer patients have the same issue. You want to stop the cancer coming back. One way you can think about this is that, for people who've had cancer and it's been cut out, you would hope that, if you vaccinate them, the cancer may not come back or their chances reduce. It basically is a way of promoting the immune response to help you recognise that cancer to control it.
Chris - One of the first recommendations you lay out is to say, let's build on what we learned about vaccines from the pandemic. Are you specifically pointing to mRNA vaccine technology with that?
Len - Yes, definitely. So that was a technology which we didn't know we could have, or use, or would be effective, and that within a year had gone from being on people's drawing boards to being given to hundreds of millions of people across the world and it gave people freedoms which we didn't expect, but it worked. When we think about leveraging the confidence of this success, it's really in two ways. The first one is, take your technology, you know you can update it from an alpha to beta vaccine really quickly, now change the little bit in the middle and put a cancer epitope there, or something that cancer looks like so the body can recognise that cancer. The second bit is, you know you can develop products very quickly, take that confidence, all the streamlined processes, and deploy it in the cancer world now and see how quickly discoveries can be made and products can be tested. Because at the end of the day, if you take that confidence of speed and all these modern ways of doing trials now, you can get an answer a little bit quicker than you thought you might have done. So that's really important.
Chris - I wondered if you would go there because that was the thing that really surprised a lot of people during the pandemic, wasn't it? The fact that we went from literally a drawing board concept to needles going into people's arms and liberating them from the shackles of Covid in months. And people were saying, look, this would normally take years of trials. Where have the corners been cut? So it was presumably a streamlining process that went into that and you are saying, well we need to make sure we don't lose sight of that and go back to the bad old days.
Len - That's the thing, isn't it? If you believe what was said before 2020, you would believe that it takes 10 years to get anything through, maybe 20 years. In fact, if you had a drug now it should take until around the 2040s before you can help a patient. Really the thinking has now changed, because actually trials and discoveries are made as quickly as people are entered into trials and patients want to take part. And actually it's the streamlining of the processes, but also greater participation and awareness that enables you to go faster.
Chris - One of the other things on your list of recommendations is the infrastructure, and how we approach doing trials. Presumably, the fact that we are now into an era where the electronic patient record is very much the mainstay of how we operate medically, it gives us much better control of the data. And then you can bring in other insights like AI to begin to pick through all those data points and you go from trials that would've had thousands of people in them to trials with billions of data points. That must make things more agile?
Len - It does indeed. That's the strength of what we created in the UK because all nations were tested, but actually the ones which can use the electronic patient records the best were the ones which were able to make greater strides. The world looks at the UK as being the place where, every month, discoveries were made. And you've got to think about why that is. I think it's probably because of the NHS. We've got the data systems so you can work out when they needed scans, what did the scans show, what happened, and ultimately what their outcomes were. That sort of trials infrastructure, based around modern healthcare records, is the way forward and, really, ones we should be investing more in to try and get the greatest benefit.
Chris - Whose desk do you hope these recommendations land on? In other words, who are they actually arguing at or hopefully influencing so that these sorts of things can be achieved?
Len - Good question, Chris. This was written to target a broad audience actually because, at the end of the day, if people want an agenda to succeed, and patients put themselves forward and doctors offer them trials and the hospitals open up, that is all that's required. Hospitals, patients, and their doctors. I think ultimately it's an awareness piece. But at the end of the day, if we do the small things, which is what everyone can do, which is that if you are a cancer doctor to open the trial, if you are a member of the public to be aware of this and support this and mention it and talk about it amongst friends, and, for hospitals, to open up, then that will happen. And actually early indications show we've ended up doing really, really well. Some of our fantastic centres are opening up very, very quickly now with the confidence that they could succeed. We are gradually growing up that recruitment global charts. We've become actually a very good centre for cancer vaccine research, if not the best.
13:48 - Competency-based medical training
Competency-based medical training
Gloria Pedersen, Harvard Medical School
Health systems rely on competent workers. So why are the majority of training programmes biased heavily towards knowledge-based assessments, rather than tests of actual competency? It sounds obvious when you put it like that doesn’t it, so can we do it better? Gloria Pedersen, from Harvard Medical School, thinks we can, and, as she explains to Chris Smith, she’s been evaluating the effectiveness of a competency-based programme for trainers and supervisors in Nepal, Peru, and Uganda…
Gloria - Globally, there is a growing demand to meet mental health needs and also to improve the quality of healthcare delivery overall. But right now the workforce just really isn't skilled in certain aspects such as foundational helping skills (like effective communication, empathy, promoting hope for change) that really ensure safe and effective service delivery. In fact, 98% of the healthcare workers scored harmfully in these competencies before taking part in our training, suggesting that existing education is falling short either by not covering these skills, or are focusing too heavily on knowledge-based learning rather than practical competency.
Chris - Does this mean then that what we regard as our gold standard curriculum isn't fit for purpose? The way we're currently training people to do this isn't up to scratch?
Gloria - How we're training isn't up to scratch. I think what we're learning is that everything's really being taught more in a knowledge based approach. People are using knowledge multiple choice questions to determine whether or not these skills are set, so I think really this idea of having a more tailored approach rather than a one size fits all training, one that's really interactive (using roleplay, having competency assessments with tailored feedback on how folks are doing) can really elevate the rate at which folks reach competency in these skills as well as the efficiency with which they reach them.
Chris - You're advocating then more for a bit like doing a driving test for this sort of healthcare provision, rather than I demonstrate that I've learned all the things that Freud said and thought, and I can reproduce them in an exam but I've never been near a patient. You are saying we need to make sure that people, when they are going near a patient, not only know all the stuff that Freud said, but also know how to use that information in a way that's meaningful and impactful for the patient.
Gloria - Exactly. Actually, the roleplays do just that where it gives them the opportunity to practise with someone who's pretending to be the patient or the person they're working with, as well as having a tool that specifically lists out behaviours that are describing what we want to see and show when we're having that engagement.
Chris - Just playing devil's advocate for a moment, though, Gloria, how do we know that that's any better and we'll end up with better outcomes than what we've got at the moment?
Gloria - I think that's a really great question and still one that we're investigating in terms of patient outcomes, but what we have seen in most research that's come out is that roleplay based competency assessment, compared to knowledge-based assessment, does predict better outcomes in patients. Ultimately, there is still some work to be done in terms of looking specifically at patient outcomes, but what we can say is that for sure this is a promising route for ensuring a 'do no harm' approach among these providers.
Chris - What about the healthcare workers themselves? If you ask them both before and after when you start working on them in a competency based way, rather than just the 'have you reach the required level of knowledge' way, do they feel more empowered? Do they feel they're doing better by their patients when they're armed with your approach compared to what I'll call the 'traditional' way of doing it?
Gloria - That was one of the most exciting things from this study is that that's exactly what we heard and learned from these folks. The interactive style, particularly due to the roleplay practice and the feedback, really highlighted the difference from what they had learned in their typical training. We heard from an obstetrician who takes a typical mental health training for a suicide assessment as part of their pre-service training leading up to them being an obstetrician. We can compare that to what they learned and how they learned how to practise it in this training, and they let us know a few weeks later that they have now felt more confident to bring it up actively with their patients. They're talking about the topic of suicide. Their patients are opening up more and all because they really didn't even understand that: 'Well, I understand the questions are there, but I didn't know I'm supposed to ask them directly or how I should do that.' We are hearing it from the health workers and, even beyond that, we're hearing overwhelmingly from these health workers that were trained just how excited and impacted they felt based on it. How they can't wait to see what changes this is going to make with their patients. They want to get more feedback on how this might be making them treat overall holistically this person rather than just another checkbox in terms of treatment.
Chris - What about implementation? Because obviously there's practising like this, but then there's teaching people to practise like this, and then there's teaching people to teach how you practise like this. So what do you think the barriers now are to implementing this and how realisable is it?
Gloria - That's a really important question. For one, the manual that we designed actually is specifically for just that: how trainers and supervisors alike can teach these skills using these competency-based approaches like the roleplays and feedback and tools. That being said, our trainers in this study, some were a little bit more experienced, others weren't as much. So, it does take some time. We also learned that, particularly for the trainees who were currently delivering services - they were going to work during the day (like nurses) and then at night take this training - ultimately, to really optimise the tools and the modular approach of this foundational helping skills training, it could be best implemented into a pre-service or into a school setting where a nurse is already there to learn about all of her techniques in addition to the specific style of competency-based training approaches. I would say that there are definitely barriers when it comes to time and resources, but we also learned and are learning currently from some of our partners in Uganda and in Peru ways that this could also be included in a more simple fashion. For example, in this study, we had actually done a full 8 to 10 modules of training in 20 hours, whereas for the manual setup you could just do one module, looking at it sort of as a continuing education, or just embedding it in ongoing monitoring and supervision.
20:41 - Consequences of large animal extinctions
Consequences of large animal extinctions
Jens Christian Svenning, Aarhus University
Across the last 50,000 years or so, the planet has lost the majority of its large animals, known as megafauna, from most of its landmasses. It’s tempting to blame the climate, or just evolution’s natural ebb and flow, but those familiar with the timeline will recognise that this disappearance coincides with our ascendency, putting us squarely in the frame. Presenting to Chris Smith the case against us, and the consequences, is Aarhus University’s Jens Christian Svenning…
Jens - If you're interested in prehistory, one thing that really stands out is that large animals used to be all over nature on all continents, whether dry, wet, cold, warm. The situation nowadays, where the biggest animals we have in nature are usually some kind of deer or something like that, it's really unusual. That's my starting point.
Chris - And what do you define as a large animal, then? Are we talking elephant size or, you highlight deer, just bigger than a deer?
Jens - Animals come in all kinds of body sizes. A classical definition is that they should have a body weight of at least 45 kilos or 100 pounds. That's still pretty arbitrary, but a sizeable animal like a fallow deer.
Chris - And if one looks back in the fossil record, is there evidence that it was the case that they were everywhere and now they're not? Or have they always been in this fairly restricted distribution?
Jens - No. Big animals and even the very big, so elephant sized, were all over the place until very recently in pre-history, let's say, 10,000 to 30,000 years ago. If you go into any good natural history museum in North America or in Europe or in Asia or in Africa, you'll find elephants from these timescales. You see that these kinds of animals were there. And in fact, we had 15 species of elephants from Patagonia to Alaska, from Alaska to Britain, and from Britain to the Cape, until 30,000 years ago.
Chris - And when did they start to decline?
Jens - They started to decline roughly 30,000 - 50,000 years ago. And then it kept going until 12 out of 15 species went completely extinct.
Chris - The timeline that you've highlighted does map onto when we've seen some climatic changes on Earth. Can we explain this loss in the same way as we've seen boom and bust for all kinds of species over Earth's evolutionary history and just say, well, this is down to some kind of changing environment and that's why these animals have gone. The niche that they occupied has been snatched away by climate change?
Jens - No, we actually can't explain this from climate. It's very clear, in fact. In the last million years we've had these very strong climatic cycles with ice ages and warm periods like the present coming and going with a timing of 100,000 years. We've had 10 of those cycles roughly. Elephants did very well through these cycles until the last 50,000 years. That makes good sense because elephants are super generalised animals that can eat all kinds of vegetation. We had elephants from super cold areas, like arctic areas, to the warmest areas, and from desert-like areas, through forest areas. They were all over the place and very generalised, so you can't explain this from climate.
Chris - So if it isn't climate, what do you think has led to the decline in not just elephants but these big animals in general and everywhere?
Jens - The explanation is clearly with ourselves, our species. We see this decline really starting with the emergence of really modern people and then the expansion across the planet. Then we see very consistently these declines in elephants and in all kinds of other big animals. If we look in detail at the archaeological evidence, we can also see that our ancestors were hunting mammoths and other elephants, made big traps and were able to kill really big individuals or even whole flocks. We can also see from their bones that they had a large amount of their protein often coming from elephants and rhinos and so on.
Chris - And is that why the loss is chiefly focused then on these big animals rather than the smaller ones? Because those were the ones that our ancestors were going after?
Jens - Yes. If you go out hunting and you could get a big animal like a mammoth or something like that, that would give food for your family and the people in your tribe for quite a long time and would be a very efficient use of your energy relative to trying to hunt smaller animals, which could be equally difficult to kill.
Chris - People often say that these big animals deliver a lot of ecosystem services. They're effectively farmers for us. And if they're not there, you don't have those services. What have been the consequences then of the loss of these big animals from nature over this time period?
Jens - The consequences are likely fundamental. It is something that we are still working on, but it's very clear from both first principles but also from empirical evidence that this has had big consequences. First of all, the larger animals interact very strongly with vegetation. They eat plants, elephants tumble over trees, they generate pathways and so on. We can see actually that European forests, for example, before the extinction of these large animals, was really a mix of, say, classical tall forests, really disturbed vegetation, and even open vegetation. And it's very hard to explain this other than from the effects of these animals. They likely had really strong impacts on the ecosystems; changing vegetation, controlling fire regimes, and also dispersing lots of other species around.
Chris - So what differences does the world display today? When we look at the world around us today, how different does it look because these animals are now missing, do you think?
Jens - Well, of course, the place to look is in our natural areas because the rest we have fundamentally changed in other ways. Of course that deviates completely from the natural state. But even if you go into our natural areas, they deviate strongly from what was normal if you look into prehistory. In Europe, I would say you very often find much denser forests than you otherwise would find. It's not that we wouldn't have lots of trees, but it would be a much more mixed landscape than we usually find today in those kinds of settings.
Chris - And hence, if we've changed the environment because we don't have these big animals, there must be knock on consequences for other animals that we don't go hunting because their environment has changed?
Jens - Yes, there are likely lots of consequences. Of course, many other animals directly depend on the large animals, like dung beetles or scavenging birds and so on, and we actually do see big extinctions in scavenging birds associated with megafauna, large animal declines. But also, lots of forest plants actually associated with quite high light levels, they really suffer in modern dense forests. That's another example that they're missing something to keep the system more varied, more open. We also see that lots of plants are very strongly dispersed and limited in our natural landscapes today, and they really miss the animals to move them around.
Chris - Us humans are not really good news for the planet, are we?
Jens - We haven't been very good news for the other species, no. But of course we have the ability to think and rethink and that's something we can still do. I would say there's a way forward. I don't think it's about going back, but we can definitely restore the large animals. Many of the species are not extinct and if we give them the chance, they can rebound, they can come back. Not necessarily the exact same species, but at least other large animals in our systems. That would be really good for the functioning of our ecosystems.
28:21 - Resilience in future water supplies
Resilience in future water supplies
Sunhil Sinha, Virginia Tech
Water is our most precious resource: drinking water and wastewater services sustain core functions of society, and of course human life itself. But our water systems are dogged by ageing infrastructure, floods, droughts, storms, earthquakes, sea level rise, population growth, pollution, and even cyber-security breaches. And speaking with Chris Smith is the man who worries about all of this, and tries to develop strategies to surmount these problems, Virginia Tech’s Sunhil Sinha…
Sunil - The problem we are addressing here is related to water infrastructure. A lot of people don't realise how water comes to their tap or, when they floss, what happens. There is an infrastructure which takes care of drinking water, wastewater, storm water. The challenge we are facing is because of climate change and also ageing infrastructure. How do we make this infrastructure more sustainable and resilient?
Chris - That's going to vary depending upon whether I'm talking about, say, London, somewhere in the US, or rural India, isn't it?
Sunil - Yes. But, firstly, we are talking about making this infrastructure resilient. First, we need to think about why we built this infrastructure in the first place: to provide a service. A service to the citizens and a service to the economy/industry in that area, the community. Infrastructure needs to provide a service not just under normal conditions, but also under stressed and catastrophic events. So whether it is in London or in India or other developing countries, the hazards will be the same. If a hurricane is coming, a sea level rise, an earthquake, it'll impact the infrastructure. The scale will be different because if it is in a developed country, like London and in the US, the damage will be greater. Also, it depends how we build this infrastructure in the first place. So you are right, the scale, location, we have to take into consideration these multi hazards.
Chris - One thing we have to consider though is, in order to work out how big the problem is that we are grappling with, we have to understand what we have already and how big the problems are. Have we got a sort of framework already?
Sunil - No. That's a good point you raise, understanding the problem. Right now we are facing, if you look at climate change or a natural disaster, if it is coming in a 100 year or 50 year timeframe, most of the infrastructure we built is based on these conditions. But now things have changed. The baseline has changed. We are seeing these hurricanes, natural disaster frequency has increased. Intensity has also increased. It's not the same. Hurricanes are now coming every year. They are coming at level 4, 5. Now we need to think about this infrastructure, how we strengthen it, or retrofit or adapt this infrastructure. We can't build in the same way that we built this infrastructure 50 years or a 100 years back. With this new baseline, we need to think outside the box and come up with a new standard, new design practices. How are we going to build this infrastructure, also, how are we going to retrofit, because we are not going to build everything from scratch. That's important. You brought up the question of developing countries. In developing countries, they are building a lot of this infrastructure, so they need to consider this when they are building this new infrastructure. How are they are going to sustain and also make it more resilient so that it can provide a service not just for this generation, but for your kids and grandkids.
Chris - How good are we, though, at anticipating the threats ahead? I'll give you an example. The population of the UK has risen by millions in the last couple of decades, largely driven by migration. There's now a housing crisis and people are saying, let's just build more houses. But at the same time people are turning around and saying, but what are the people who live in these houses going to drink? Because no one thought, well, if we bring millions in, they're going to drink millions more litres?
Sunil - That's why we need to look into a whole system approach. We can't just do it randomly, or make projections, because a lot of things are changing. You mentioned the population growth. Resilience is not just building this infrastructure and making it more robust. We can't do that. First of all, we don't know what will happen 20 years down the line, how the climate will change or what other stresses will come. These are dynamic in nature. We need to be more smart and digital technologies are helping us. In the US also, if you carefully look at the US population, it's moving where there is no water, like in Arizona and Nevada. We need to think now on a bigger scale with a whole system approach, looking at where these ageing populations are. People want to live in Florida because of the coastal areas but, with sea level rises, it's not that easy, because you can't even now buy a house in Florida and pay the insurance because insurance companies are not willing to insure it unless your house is retrofitted to a certain level. That's going to cost a lot because, now you are talking hurricane level 5, your roof will cost 10 times more. We need to be more systematic. We need to look from the whole system perspective: how are we going to make the policies and law. Not everything can be done by law. Also, we need to educate our people as to the threat we are facing, and not just short term but also long term. Education is important.
Chris - You've put forward some possible solutions there, but it seems like an enormous problem to try and grapple with, to try and do this across the entire world, and it doesn't sound like we've got very long to do this?
Sunil - But you see, we are at the tipping point. Climate change, natural disasters, every time any disaster comes to the US, it costs billions of dollars. We need to think harder about how we are designing this infrastructure. It can't be the same old story that it was a hundred years back because, as I mentioned, the baseline has changed. We need to be smart now. Fighting with Mother Nature because of climate change, we need to think about how we are designing cities and towns, how we are sustaining, maintaining it. Otherwise it'll become too costly to sustain.
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